Carcinoma of the lung is the leading cause of cancer death in men and the second leading cause of cancer death in women. Its mortality now exceeds 100,000 each year in the United States. With current methods of treatment, fewer than 10% of all lung cancer patients will be alive in five years. The vast majority die of disseminated disease within two years of diagnosis. Among all lung cancer patients we see, 85% have non-small cell lung cancer. Of this latter group, 30% have mediastinal lymph node metastases without distant metastases (TanyN2MO) at the time of initial treatment. These patients are generally regarded as incurable. In patients with mediastinal lymph node involvement, we found that aggressive local management, adding interstitial radiation (brachytherapy) to operative resection and external radiation therapy resulted in local and regional control in many cases with prolonged survival in some. In those whose disease was completely removed, combined resection and postoperative external radiation achieved a 57% two-year survival and a 44% three-year survival. Even when residual tumor was left at operation, 69% of our patients were alive at one year. These results are the best that have been reported for both local control and survival. Failure was due mostly to distant metastases. We also have found that the combination of vindesine and high-dose cisplatin provides a 43% rate of major response and prolonged survival in patients with measurable non-small cell lung cancer and toxicity has been acceptable. These results also are the best that we have achieved. It is now timely and urgent to combine these successful treatments in a clinical trial randomizing operable patients to receive vindesine and high-dose cisplatin or no chemotherapy. All local and regional disease will be treated by combined surgery and radiation therapy. It is estimated that 100 patients will enter the trial during the first three years of the study. By adding systemic chemotherapy to the aggressive local management, we seek to reduce distant metastases and thereby both lengthen the disease-free interval and improve survival beyond that achieved with aggressive local management alone.